کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6263917 1613936 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research ReportDisruption of dystroglycan-laminin interactions modulates water uptake by astrocytes
ترجمه فارسی عنوان
تحقیقات انجام شده بروز اختلالات متقابل دیاستروگلیکان-لامین می تواند جذب آب توسط آستروسیت ها را مد نظر قرار دهد
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی

Cerebral edema is a serious complication of ischemic brain injury. Cerebral edema includes accumulation of extracellular fluid due to leakage of the brain's microvessel permeability barrier, and swelling of astrocytes as they absorb water from the extracellular space. Expression of matrix adhesion receptors in brain microvessels decreases in ischemic stroke; this contributes to increased microvessel permeability and detachment of astrocytes from the extracellular matrix (ECM). Since loss of the astrocyte adhesion receptor dystroglycan has been associated with disrupted polarization of ion and water channels, we hypothesized that adhesion of astrocytes to the ECM contributes to regulation of water uptake, and that disruption of matrix adhesion impairs the ability of astrocytes to direct water transport. To test this hypothesis, the capacity of astrocytes to take up water was measured using a fluorescence self-quenching assay under both oxygen/glucose deprivation (OGD) and direct antibody-mediated blockade of α-dystroglycan. Both conditions decreased the rate of water uptake. Moreover, inhibiting proteolytic cleavage of dystroglycan that occurs in OGD abrogated the effect of OGD, but not direct blockade of α-dystroglycan, indicating that interfering with dystroglycan-matrix binding itself affects water uptake. Activation of extracellular signal-related kinase (ERK) by OGD was dependent on α-dystroglycan binding, and inhibition of ERK activity with U0126 abrogated the loss of water uptake following OGD. These studies demonstrate for the first time that water uptake in astrocytes is regulated by dystroglycan-dependent signaling associated with matrix adhesion. This presents a novel potential approach to the treatment of cerebral edema.

► Experimental ischemia (OGD) decreases the rate of water uptake in astrocytes in vitro. ► Blockade of α-dystroglycan mimics the effect of OGD on water uptake. ► ERK phosphorylation in response to OGD depends on dystroglycan binding. ► Inhibiting protease activity or ERK activation preserves water uptake in astrocytes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1503, 29 March 2013, Pages 89-96
نویسندگان
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